Mutationally activated tyrosine kinases (TK) of the epidermal growth factor receptor (EGFR) family are considered a major driver of cancer cell survival and aggressive tumor growth. In non-small cell lung cancer, expression levels of EGFR are inversely correlated with survival of the disease. Somatic (activating) EGFR mutations sensitize cancer cells to small-molecule tyrosine kinase inhibitors (TKIs), which target the enzyme's ATP binding site and show potent antiproliferative properties. Gefitinib is a quinazoline-based TKI indicated against cancers harboring aberrant EGFR, in particular lung carcinomas. Unfortunately, the efficacy of this drug is limited by the emergence of acquired resistance as a consequence of a secondary mutation within the ATP binding pocket. One currently pursued approach to combatting this form of resistance observed for mutant EGFR and other clinically relevant kinases is to turn the reversible TKIs into irreversible inhibitors (ITKIs). These molecules contain a strategically positioned reactive electrophilic group (usually a Michael acceptor), which is able to form a covalent bond with accessible cysteine residues in the active sites of the targetable enzymes.